Alkyl-or aryl-mercapto-(sulphoxido-, sulphono-) carboxylic acid derivatives of thiophosphoric, thiophosphonic and thiophosphinic acid esters and processes for their production



United States Patent 3,229,000 ALKYL- 0R ARYL-MERCAPTO-(SULPHOXIDO-,

SULPHQNOQ CARBOXYLIC ACHD DERIVA- TIVES OF THIGPHQSPHOREC, THIOPHOS- PHONIC AND THIOPHOSPHINIC ACID ESTERS AND PRGCESSES FOR THEIR PRODUCTION Walter Lorenz, Wuppertal-Vohwinkel, Hans-Gerri Schiclre, Wuppertal-Elberfeld; and Gerhard Sehrader, Wnppertal-Cronenberg, Germany, assignors to Farbenfabriken Bayer Aktiengesellschaft, Leverkusen, Germany, a corporation of Germany No Drawing. Filed Apr. 26, 1963, Ser. No. 276,087 Claims. (Cl. 260-943) This application is a continuation-in-part of applications Serial No. 83,888, filed January 23, 1961, now abandoned, and Serial No. 186,338, filed April 10, 1962, now abandoned.

The present invention relates to and has as its objects new and useful insecticidal thioor dithiophosphoric, phosphonic and -phosphinic acid derivatives and processes for their preparation. The new compounds of this invention may be represented by the following general formula They possess an outsanding insecticidal activity and are consequently suitable for controlling insect pests. Furthermore, they are surprisingly much less toxic to warm-blooded animals than are the closest compounds of the prior art, as exemplified'in US. Patent No. 2,815,312.

In this formula, R stands for an optionally substituted alkylor aryl-radical, R is hydrogen or an alkyl radical,

R and R stand for radicals which together with the.

R S-R wherein R and R are low molecular aliphatic hydrocarbon radicals, R is an alkyl or aralkyl radical which may be substituted, R stands for --COOR CON or CEN, each of R R and R being a low molecular aliphatic hydrocarbon radical, and Y stands for O or S.

From oopending US. patent application Ser. No. 83,888 there are known thioor dithio-phosphoric-(onicor inic) acid derivatives of the general formula in which R stands for an optionally substituted alkylor aryl-radical, R is hydrogen or an alkyl radical, R and R stand for radicals which together with the remaining molecule residue form a derivative of a thioor dithiophosphoric-( onic) acid ester or amide or a thioor dithiolCe phosphinic acid ester, while X represents a carboxylic acid ester-, amide-, or nitrile-group, Y stands for oxygen or sulphurs and n is zero, 1 or 2.

The compounds of the above general formula are dis tinguished by a good insecticidal and partly also by a systemic effect against a series of pest insects, and are, therefore, intended to be applied as pest control agents, mainly in plant protection.

In accordance with the present invention it has now been found that carboxylic acid amides of the formula possess an outstanding insecticidal activity and are consequently suitable for controlling insect pests, particularly in view of their considerably reduced toxicity to Wannblooded animals.

In the last mentioned formula, R, R R R Y and n have the same meaning as given further above, while 'R' is hydrogen or an alkyl radical R" and R' stand for-optionally substituted alkyl, cycloalkyl-, aralkylor aryl-radicals or can form with the nitrogen atom aheterocyclic ring system which may be interrupted by further heteroatoms; R" can also be hydrogen.

The production of the compounds according to the invention proceeds in an analogous manner to that described in the main patent, i.e. by addition of optionally substituted alkylor aryl-sulphenic acid halides to afi-llnsaturated N-alkyl-, N-cycloalkyl-, N-aralkylor N-arylcarboxylic acid amides followed by reaction of the N- substituted a-alkylor a-aryl-mercapto-p-halocarboxylic acid amides formed, with salts of thioor dithio-tphosphoric-(onic) acid esters or acid. amides or of thioor dithio-phosphinic acids, and, if desired, subsequent oxidation of the resulting phosphorous-containing a-alkylor a-aryl-mecapto carboxylic acid derivatives, to the corresponding suliphoxidoor sulphono-compounds.

It is also possible, however, first to oxidise the N-substituted a-alkylor a-aryl mercapto-B-halocarboxylic acid amides eg with hydrogen peroxide, nitric acid, hypohalogenous acids, potassium permanganate or similar oxidising agents, to the corresponding ii-halogen-sulphoxides or -sulphones and to react these further in the aforementioned way.

The following scheme illustrates the process according to the invention in more detail:

I-Ial SR In the foregoing formulae R, R, R, R, R R R and Y have the significances given above, while Hal stands for a halogen atom, n is equal to 1 or 2 and Me is an alkali metal, alkaline earth metal or ammonium ion.

The reactions according to the present invention are preferably conducted at elevated temperature (50 to C.) and with the use of inert organic solvents. Lower aliphatic nitriles, e .g. acetonitrile, have proved especially suitable for this purpose. Furthermore, for the purpose of completing the reaction, and thus for achieving good yields, it is expedient to after-heat the reaction mixture after combining the starting components for a while (1 to 3 hours). The a-alkyl or a-aryl mercapto-(sulphoxidoor sulphono-) carboxylic acid derivatives obtainable according to the process of the invention, represent partly crystalline substances, partly colourless to Weakly coloured oils mostly not distillable even in high vacuum. I

The new compounds of the present invention very effectively kill insects like flies, mites, aphids, etc. They distinguish themselves especially by a good contactinsecticidal activity and at the same time by an activity on eating insects such as caterpillars. They may be used in the same manner as other known phosphoric acid insecticides, i.e. in a concentration from about 0.00001% to about 1%, diluted or extended with suitable solid or liquid carriers or diluents.

Examples of such solid carriers are talc, chalk, bentonite, clay and the like, as liquid carriers there may be mentioned water (if necessary with commercial emulsifiers), alcohols, especially lower alcohols such as meth anol or ethanol, ketones, especially lower ketones such as acetone or methyl ethyl ketone, liquid hydrocarbons and the like. The new compounds may furthermore be used in combination with each other or with known insecticides, fertilizers etc.

As an example for the special utility of the inventive compounds the ester of the following formula CzHgO O O 211 O S C 2115 has been tested against aphids and spider mites. Aqueous solutions of the aforementioned compound have been prepared by admixing them with the same amount of an auxiliary solvent (acetone). A commercial emulsifier (benzyl hydroxy diphenyl polyglycol ether) is added in an amount of 20% referred to active ingredient. This premixture then is diluted with water to the desired concentration. The tests have been carried out as follows:

(a) Against aphids (contact-insecticidal action) of the type Doralis fabae. Heavily infested bean plants (Vicia faba) have been sprayed drip wet with solutions as prepared above. The eifect has been determined by evaluation after 24 hours by counting the dead pests either on the surface of the soil or still remaining on the plants. The following result has been obtained:

Aphids are killed completely with 0.001% solutions.

(b) Against spider mites (contact-insecticidal action). Bean plants (Phaseolus vulgaris) of about 15 inches height are sprayed drip wet with solutions prepared as indicated above. The bean plants have been infested heavily with the two-spotted spider (species Tetranychus telarz'us). Evaluation has been carried out after 24 hours, 48 hours, 8 days. The following results have been obtained:

Spider mites are killed completely with 0.001% solutions.

The following examples illustrate the process according to the invention:

Example Ia Cl-CH2-CH-CO-NH.CH3

234 g. of ethyl sulphenic acid chloride dissolved in 500 cc. of carbon tetrachloride are added dropwise at 20 C. to a solution of 203 g. (2.5 mol) of acrylic acid N-monomethylamide in 500 cc. of carbon tetrachloride, the mixture is stirred for a further hour at 20 C. and the solvent distilled oif in vacuum. The remaining res idue crystallizes after standing for a short time and can berecrystallized from an ether/ petroleum ether mixture.

4 t 410 g. are obtained (91% of the theoretical) of methylmercapto-B-chloropropionic acid N-monomethylamide, of M.P. 50 C.

Example 1b Call-I 0 S C2115 61 g. (0.3 mol) of 0,0-diethylthionothiolphosphoric acid ammonium salt are dissolved in 250 cc. of acetonitrile. To this solution asolution is added dropwise at 70 to C. of 54 g. of ot-ethylmercapto-fi-chloropropionic acid N-monomethylamide in cc. of acetonitrile, the reaction mixture is warmed for an hour to 70 to 80 C. and poured after cooling to room temperature, into .100 cc. of water. The separated oil'is taken up in methylene chloride, the methylene chloride solution is washed with water and dried over sodium sulphate. After evaporating the solvent the residue crystallizes from an ether/petroleum ether mixture. Yield: 70 g. (70.5% of the theoretical) of 0,0-diethylthionothiolphosphoric acid-S-(fi-ethylmercapto, B-N-methylaminocarbony1-ethyl)ester of MP. 64 to 65 C. The compound shows an ovicidal action against the eggs of the red spider. Aphids are killed completely with 0.001% solutions. Spider mites are 60% killed with 0.001% solution.

In an analogous manner, as described in Example 1b,

the following compounds can be produced.

Physical properties and Constitution M.P., C.

where applicable Aphids are-killed completely with 0.001% solutions. Caterpillars are killed completely with 0.1% solution.

Aphids are killed completely with 0.01% solutions. Systemic action with aphids on oats 0.1%=100% killing.

CH3 SCzHs Aphids are killed completely with 0.001% solutions. Mosquito larvae are killed to 100% with 0.0001% C2115 S (12H;

'Aphids are killed completely with 0.1% solutions.

Systemic action with aphids on oats killing.

Example 2::

Under analogous reaction conditions to those described in Example 1a, there are obtained from 218 g. (2.2 mol) of methacrylic acid N-monomethylamide and 212 g. of ethylsulfenic acid chloride, 365 g. (85% of the theoretical) of ot-methyl-a-ethylmercapto-B-chloro-pro pionic acid N-monomethylamide of 13.1. 132 C./6-7 mm. Hg.

A solution of 37 g. (0.2 mol). of 0,0-diethylthiolphosphoric acid ammonium salt in 200 cc. acetonitrile are treated at 70 to 80 C. with 49 grams of u-methyl-aethyl-mereapto-fi-chloropropionic acid N-monornethylamide, dissolved in 50 cc. of acetonitrile, the mixture is stirred for a further hour at 70 to 80 C. and poured after cooling to room temperature, into water. The separated oil is taken up in methylene chloride. After drying the methylene chloride solution over sodium sulfate the solvent is distilled oil and I55 g. are obtained (84% of the theoretical) of 0,0-diethylthiolphosphoric acid- S B methyl fl ethylrnercapto B N methylarninocarbonylethyl)-ester in the form of a weakly brown oil. Aphids and spider mites are killed completely with 0.001% solutions. The compound has an ovicidal action against the eggs of the red spider.

Analysis.Calculated for a molecular Weight of 329: P, 9.43%; S, 19.45%; N, 4.26%. Found: P, 9.19%; S, 19.42%; N, 4.19%.

In corresponding ways the following products may be prepared:

CHQO i (311 PSCH2CCONHCH Oil.

C1130 SCZH5 Toxicity on rats per os LD 100 mg./kg. Caterpillars are killed completely with 0.1% solutions. Spider mites are killed completely with 0.001% solutions and aphids are killed completely with 0.01% solutions.

Spider mites are killed completely with 0.01% solutions. The compound shows an ovicidal action against the eggs of the red spider. Aphids are killed completely with 0.01% solutions.

P-SCHz-(I]-CONH.CH3 Oil. C2 50 S O2 5 Spider mites are 60% killed with 0.000170 solution. Caterpillars are killed completely With 0.01% solution.

The compound shows an ovicidal action against the eggs of the red spider.

CZH5O fi CH3 PSCH2C|CONH-CH3 Oil. CH3 $02115 Aphids are 70% killed with 0.001% solution. Spider mites are 60% killed with 0.0001% solution. The compound shows an ovicidal action against the eggs of the red spider.

Aphids are killed completely with 0.001% solutions. Spider :mites are killed completely with 0.001% solutions. The compound shows an ovicida'l action against the eggs of the red spider.

PSCH2CCONH.CH3 Oil.

CH3 S 02115 Spider mites are killed completely with 0.01% solutions. Caterpillars are killed completely with 0.01% solutions.

CZH fi (3H3 PSCH2(]3OONH.OH3 Oil. C2115 SCZH5 Caterpillars are killed completely with 0.1% solutions. Systemic action with aphids on oats 0.1%=100% killing.

Example 3a In a manner corresponding to that described in Example la the following compounds can be obtained:

37.5 g. (0.2 mmol) of 0,0-diethylthiolphosphoric acid ammonium salt are dissolved in 250 cc. of acetonitrile, and a solution of 44.5 of a-ethylmercapto-fi-chloropropionic acid N-tert.butylamine in 100 cc. of acetonitrile is added dropwise at 70 to C., the mixture is stirred for a further hour at the given temperature and then worked up as described in Example lb or 2b. There are obtained 60 g. (84% 0f the theoretical) of Qo-diethylthiolphosphoric a'cid-S-(fi-ethykmercalpto, fl-N-tert-butylaminocarbonyl-ethyD-ester in the form of a weakly yellowish oil.

Aphids are killed completely 'with 0.0001% solutions. Spider mites are killed completely with 0 .01% solutions and 0.004% respectively. The compound shows an Ovicidal action against the eggs of the red spider.

Aphids are killed completely with 0.01% solutions. Spider mites are killed completely with 0.01% .solutions.

PSCH2-CHC ONH-C (OHM (321150 SIO2HE Aphids are killed completely with 0.01% solutions. Spider mites are killed completely with 0.01% solutions.

CHQO o t" soH2OHo O-NHC (CH3);

c1130 C211 Aphids are killed completely with 0.01% solutions. Caterpillars are killed completely With 0.1 solutions.

ll? SCHg-CHCONHC(CHs)3 01130 802115 Aphids are killed completely with 0.01% solutions. Systemic action with aphids on oats 0.1%=100% killing.

P-SCH2CHCONHC(CH3)3 c1130 SCHs Aphids are killed completely with 0.01% solutions. Caterpillars are killed completely with 0.1% solutions.

l SCHzCHC ONHC(CH 0 11 0 SCH:

Aphids are killed completely with 0.01% solutions. Systemic action with aphids on oats 0.1%=100% killing. Toxicity on rats per os LD rug/kg.

(321150 SCH3 By oxidising the compound of Example 1b with about the calculating molecular amount of 30% hydroxide peroxide solution in glacial acetic acid there is obtained the following compound in almost quantitative yields in the form of a colourless undistilled oil.

Oxidation of the compound of Example lb or of the aforementioned sulphoxide with about the calculating amount of potassium permanganate in aqueous acetonic solution the lower temperatures around 0 C. there is obtained in almost quantitative yields the corresponding sulphone of the ttollowing formula As described in Example 1a there are obtained 226 g. of u-methyl-u-methylmercapto ,B-chloro-propionic acid morpholide in the form of a colorless oil from 155 g. (1 mol) of methacrylic acid morpholide and 82.5 grams (1 mol) of methyl-sulfenic acid chloride. Yield 94% of the theoretical.

37.5 g. (0.2 mol) of the ammonium salt of diethylthiolphosphoric acid are dissolved in 150 cc. of acetonitrile. Thereto are added dropwise at 7080 C. 47.5 g. of u-methyl-u-methylmercapto p-chloro-vpropionic acid morpholide in cc. of acetonitrile. The mixture is stirred for 1 hour at 70-80 C., and then cooled down to 20 C. The separated ammonium chloride is filtered off with suction. The solvent is distilled oil in vacuum and the remaining parts taken up in methylen chloride, washed with water and dried. After separation of the solvent there is obtained a tough light yellow oil.

Analysis.Calculated for mol 271: P, 8.35%; S, 17.25%; N, 3.78%. Found: P. 7.99%; S, 17.10%; N, 3.81%.

Example 5a From 113 g. (0.8 mol) of methacrylic acid diethylamide and 77 g. of ethyl-sulfenic acid chloride there are obtained as described in Example 1. 129 grams of a-methyl-a-ethylmercapto-B-chloroepropionic acid diethylamide in the form of a colorless oil. Yield 68% of the theoretical.

To a solution of 24 g. (0.15 mol) of the ammonium salt of dimethylthiolp'hosphoric acid in 200 cc. of acetonitrile there is added dropwise at 7080 C. a solution of 35.5 g. of u-methyl m-ethylmercapto-fl-chloro-propionic acid diethylamide in 100 cc. of acetonitrile. Stirring is continued for 1 hour at 7080 C., and the mixture then is cooled down to 20 C., the separated crystals are filtered off with suction andthe acetonitrile is separated by distillation in vacuum. The residue is taken up in methylen chloride, washed with water and dried. The solvent is then distilled off. There are obtained 37 g. of a yellow oil. Yield 72% of the theoretical.

Analysis.Calculated for mol 343: P, 9.04%; S, 18.68%; N, 4.05%. Found: P, 9.24%; S, 18.45%; N, 4.12%.

Example 6a ClCHOHCONHCIIa As described in the foregoing examples, there are obtained from 168 g. (1.7 mol) of crotonic acid monomethylamide and 164 g. of ethylsulfenic acid chloride 252 g. of m-ethylmercapto-fi-chloro-butyric acid monomethylamide. Yield: 76% of the theoretical.

Example 619 CH3O H3 CZHE To a solution of 35 g. (0.2 mol) of the ammonium salt of dimethyldithiophosphoric acid in cc. of acetonitrile there are added dropwise at 7080 C. 39 g. of a-ethylmercapto-B-chloro-butyric acid monomethylamide in 100 cc. of acetonitrile. The mixture is afterstirred for 1 hour, cooled down to 20 C. and then poured into water. The separated oil is taken up in methylenchloride and dried over sodium sulfate. After distilling 01f the solvent there is obtained a brown-yellow oil. Yield: 41 g.=65% of the theoretical.

Analysis.-Calc ulated -for mol 317: P, 8.79%; S, 30.25%; N, 4.42%. Found: P, 8.16%; S, 29.85%; N, 4.59%.

What is claimed is: 1. A compound of the formula R2 Y R R II I in which R stands for lower alkyl having up to 4 carbon atoms; R stands for a member selected from the group consisting of hydrogen and lower alkyl having up to 4 carbon atoms; R and R stand for a member selected from the group consisting of lower alkyl and lower alkoxy, both lower alkyl and lower alkoxy having up to 4 carbon atoms; R stands for a member selected from the group consisting of hydrogen and lower alkyl having up to 4 carbon atoms; R" stands for a member selected from the group consisting of hydrogen and alkyl; R' stands for alkyl; and R" together with R and N stand for morpholino; n stands'for a whole number between and 2; and Y stands for a member selected from the group consisting of oxygen and sulfur.

2. A compound. of claim 1 wherein R and R are each lower alkoxy; R R and R are each hydrogen; and R and R are each lower alkyl.

3. A compound of claim 1 wherein R is lower alkoxy; R R and R are each lower alkyl; and R R and R" are each hydrogen.

4. A compound of claim 1 wherein R and R are each lower alkoxy; R, R and R are each lower alkyl; and R and R" are each hydrogen.

10 5. A compound of claim 1 wherein R R R, R and R' are each lower alkyl and R and R" are each hydrogen. 6. The compound of the following formula CzHgO S \ll P-S--CHCHCO-NH-CH;

7. A compound of the following formula 8. A compound of the following formula 9. A compound of the following formula 10. A compound of the following formula P-SCHzCH-CONHC(CH3):

CzHs scz s References Cited by the Examiner UNITED STATES PATENTS 2,815,312 12/1957 Schuler 260461 CHARLES B. PARKER, Primary Examiner. 

1. A COMPOUND OF THE FORMULA 